We wish to determine the extent to which the reactions of bisulfite (the aqueous form of sulfur dioxide) with nucleic acids contribute to the biological damage caused by sulfur dioxide. In the coming year, we will pursue the following goals. a) The cross-linking of DNA to histones in DNA-histone complexes, and of DNA to protein in chromatin by bisulfite will be attempted. If this is successful, the identity of the proteins crosslinked, dependence on bisulfite concentration, and other parameters of the reaction will be explored. Crosslinking of RNA and protein in ribosomes may also be examined. b) Mechanistic studies of the deamination of cytosine will be completed, and the reactivity of single and double stranded DNA to deamination under physiological conditions will be measured as accurately as possible. In order to measure the effects of very low levels of reaction, we will devise an assay to detect small amounts of deoxyuridine in thymidine. This assay will depend upon exchange of the S-hydrogen for tritium. c) Transamination studies with aromatic amines will be continued. The physical and biological properties of modified DNA will be examined. BIBLIOGRAPHIC REFERENCES: "Modification of E. coli ribosomes and coliphage MS2 RNA by bisulfite: effects on ribosomal binding and protein synthesis," B. Braverman, R. Shapiro and W. Szer, Nucleic Acids Res. 2, 501 (1975) "On the possibility of environmental mutagenesis by bisulfite;" R. Shapiro and J.B. Louis, Mutation Reg. 31,327 (1975).